AB1152 COVID-19 mRNA VACCINE BOOSTER IN PATIENTS WITH SYSTEMIC AUTOIMMUNE DISEASES
Authors: C. Cardelli, T. Caruso, C. Tani, F. Pratesi, R. Talarico, F. DI Cianni, N. Italiano, E. Laurino, M. Moretti, G. Cascarano, M. Diomedi, L. Gualtieri, R. D’urzo, P. Migliorini, M. Mosca
Journal: Annals of the Rheumatic Diseases (2022)

Background Patients with systemic autoimmune diseases (SADs) are often treated with drugs that interfere with the immune system and previous data showed a reduced seroconversion rate after anti-SARS-CoV2 vaccine in these subjects compared to healthy controls 1 . Administration of a booster dose of the vaccine could be particularly important in these patients, but data available to date are still scarce. Objectives To evaluate the antibody response to the booster dose of mRNA SARS-CoV2 vaccine in patients with SADs and to compare it to the response after completion of the first vaccination course. Secondly, to find possible correlations between a low antibody titre and patients’ clinical features, with special regard to ongoing immunosuppressive therapies. Methods Consecutive patients with an established diagnosis of SADs undergoing SARS-CoV2 vaccine were prospectively enrolled from January 2021; among them, we selected the patients who received the third vaccination dose between September and December 2021. Demographic and clinical data were collected at enrolment (sex, age, diagnosis, disease duration, ongoing therapies, previous SARS-CoV2 infection, presence of hypogammaglobulinemia); the last three elements were reassessed at each follow-up visit. Blood samples were collected 4 weeks both after the second (W4a) and the third (W4b) dose of the vaccine; a minority of patients was also tested 12 weeks after the second dose (W12). IgG antibodies to SARS-CoV2 receptor-binding domain (RBD) and neutralizing antibodies inhibiting the interaction between RBD and angiotensin converting enzyme 2 were evaluated. IgG anti-RBD were detected by solid phase assay on plates coated with recombinant RBD, while neutralising antibodies by using the kit SPIA (Spike Protein Inhibition Assay). Cut-off values were defined as the 97.5 th percentile of a pre-vaccine healthy population. Statistical analysis was performed using IBM SPSS Statistics 20 and GraphPad Prism statistical packages. P values &lt;0.05 were considered significant. Results Forty-five patients (95.6% female; mean age ±SD 55.6±14.1 years; mean disease duration 12.9±10.6 years) were enrolled. Diagnosis was in most cases connective tissue disease (31/45, 68.9%), followed by inflammatory arthritis (11/45, 24.4%) and systemic vasculitis (3/45, 6.7%). Two patients (4.4%) had a previous SARS-CoV2 infection and three had hypogammaglobulinemia (6.7%). At the time of the second dose, 18/45 patients were treated with glucocorticoids (GCs) [mean daily 6-methylprednisolone (6MP) dose 3.9 mg (min. 2, max. 14)], 17/45 with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and 12/45 with biologic DMARDs (bDMARDs). At the third dose administration, 19/45 patients were treated with GCs [mean daily 6MP dose 4.1 mg (min. 1.5, max. 10)], 18/45 with csDMARDs and 13/45 with bDMARDs. Anti-RBD IgG were positive in 42/45 patients (93.3%) at W4a, in 16/18 (88.9%) at W12 and in 42/45 (93.3%) at W4b. Neutralizing antibodies were present in 38/45 patients (84.4%) at W4a, in 14/18 (77.8%) at W12 and in 42/45 (93.3%) at W4b. Both anti-RBD IgG titers and neutralizing antibody titers significantly increased after the third dose if compared to W4a ( p &lt;0.0001 both) (Figure 1). Interestingly, of the 7 patients who had not developed an adequate neutralizing antibody response after the first vaccination course, 5 mounted an adequate titer after the booster. Two non-responder patients were both on combination therapy (one with low dose of GCs plus mycophenolate mofetil, the other with methotrexate and infliximab). Conclusion Our data suggest that in patients with SADs there is a decline in the antibody titers developed after COVID-19 vaccination, however the booster dose is effective in restoring an adequate antibody titre. These data consolidate the importance of a booster dose of COVID-19 vaccination in patients with SADs to aid in the generation of an immune response. References [1]Jena A et al. Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: systematic review and meta-analysis. Autoimmun Rev. 2022 Acknowledgements The authors would like to thank all the patients who participated in the study and the nurses Sabrina Gori, Rosanna Lo Coco, Lucia Pedrocco, Carla Puccini, Pasqualina Semeraro, Manuela Terachi, Maria Tristano, Valentina Venturini and Catiuscia Zoina who took care of the patients. Disclosure of Interests None declared